Monopar Therapeutics And Validive In Severe Oral Mucositis

Nov. 06, 2019 10:32 PM ETMonopar Therapeutics Inc. (MNPR)AMGN


  • Monopar Therapeutics is a clinical-stage biopharma developing adrenergic receptor agonist, clonidine (Validive), for treating SOM-associated oropharyngeal cancer in response to chemoradiotherapy.
  • Oropharyngeal cancer accounts for 70% of all head and neck cancer.
  • Kepivance by Amgen was approved by the FDA in 2004 to reduce the incidence and duration of SOM in patients with certain types of blood cancer (i.e., hematologic malignancy).
  • There are no FDA-approved therapies for non-hematological-associated SOM.
  • Lead investigative drug candidate Validive is Phase 3 ready for clinical evaluation in oropharyngeal cancer patients stratified for human papilloma virus.
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Therapeutic Differentiation

Monopar Therapeutics (NASDAQ:MNPR) is a privately held, clinical-stage company that recently initiated a $40 million IPO (pending). MNPR has a diverse pipeline, including MNPR-101 and Camsirubicin (MNPR-201), in clinical development to treat diverse oncological indications. The lead investigative drug candidate, Validive (clonidine mucobuccal tablet), was in-licensed from Onxeo S.A. for the potential treatment of severe oral mucositis (SOM) in patients undergoing chemoradiotherapy for oropharyngeal cancer (OPC).

Kepivance (formerly palifermin), a recombinant human keratinocyte growth factor developed by Amgen (AMGN), remains the only FDA-approved therapy for reducing the incidence and duration of SOM in patients with certain types of blood cancer (i.e., hematologic malignancy) who are being treated with high-dose chemotherapy and radiation therapy followed by a stem cell transplant.

In the US, ~500,000 individuals are diagnosed with OM annually, and the prevalence is expected to rise in parallel with an increased incidence of head and neck cancer (HNC), which has an annual projection of 65,000.

MNPR focuses on OPC for the following reasons: (i) OPC represents the most rapidly growing sub-population of HNC almost 70% and; (ii) the effect of Validive on SOM was much greater in OPC compared to non-OPC patients in Phase 2 study.

Validive In OPC

Patients with SOM have limited oral functions, meaning that investigative drug candidates must provide clinically meaningful benefits despite this limitation. MNPR believes its Lauriad technology, developed for oral transmucosal drug delivery, is designed to overcome potential oral therapeutic delivery limitation as revealed in pharmacokinetics studies showing that it:

significantly increases the mucous and salivary concentrations of the active ingredient it contains, with decreased systemic absorption. The tablet is placed under the patient's upper lip and remains there for several hours a day, releasing the active ingredient into the saliva.

The oropharynx is comprised largely of immune tissue and includes the soft palate, the base (rear one-third) of the tongue, and the tonsils. In 2011, the adrenergic receptor signaling pathway in oral epithelial keratinocytes was reported. Alpha-2 (α2) adrenergic receptor (α2AR) consists of three homologous subtypes, α2A-, α2B-, and α2C-adrenergic receptors. Noradrenaline and adrenaline both signal through α2AR. Other agonists include clonidine and xylazine.

The finding of α2AR expression on macrophages, immune cells in the oropharynx led to the concept that catecholamine and its ligands could be involved in healing wounds within the oral cavity. Besides, Kepivance by Amgen improves SOM by stimulating the growth and development of new epithelial cells to build up the mucosal barrier.

Top line data from a Phase 2b study of Validive showed that:

The incidence of SOM (primary endpoint) was reduced by 26.3% (40% relative to placebo) in OPC patients treated with Validive (100 μg) (p=0.09 which is a meaningful trend but not statistically significant). 65.2% of OPC patients on placebo experienced severe oral mucositis compared to only 38.9% of OPC patients on Validive 100 µg.).

Validive (100 µg) reduced the risk of onset of SOM by 52% compared to placebo. Secondary endpoints of severe drinking, eating, and speaking limitations due to mouth and throat soreness (MTS) score were reduced in the Validive (100 μg) treated cohort.

A Phase 3 study will evaluate Validive compared to placebo in OPC patients stratified for human papilloma virus (HPV) status. This is because the majority (~70%) of OPC patients are HPV positive.

Market Outlook

At the end of Q2/2019, MNPR reported cash of $5.1 million. The IPO of 4,444,445 common shares has been set at $8-10. Beyond Kepivance for hematological SOM, there are no FDA-approved therapeutics for non-hematological SOM. This is an area of active clinical research as reflected in the clinical trial database. Soligenix (SNGX) and Galera Therapeutics (GRTX) have Phase 3 drug candidates in clinical development for SOM. The proceeds from the IPO provides MNPR with the funds to initiate the Phase 3 clinical development of Validive in SOM-associated OPC.

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